HK1027959B - Drug composition - Google Patents

Description

Pharmaceutical composition

Technical Field

The present invention relates to a pharmaceutical composition and a composition for a kit, which contain 2-amino-2- [ 2- (4-octylphenyl) ethyl ] propane-1, 3-diol or a pharmaceutically acceptable acid addition salt thereof as an active ingredient. More specifically, the present invention relates to a pharmaceutical composition which can be formulated into a liquid preparation, and which is characterized by containing 2-amino-2- [ 2- (4-octylphenyl) ethyl ] propane-1, 3-diol or a pharmaceutically acceptable acid addition salt thereof containing a lecithin compound and is suitable for suppressing rejection in organ (kidney, liver, heart, small intestine, etc.) or bone marrow transplantation, or for maintenance immunotherapy or treatment of autoimmune diseases.

Background

For example, international publication No. WO94/08943 discloses that 2-amino-2- [ 2- (4-octylphenyl) ethyl ] propane-1, 3-diol or a pharmaceutically acceptable acid addition salt thereof is useful as a rejection inhibitor in organ or bone marrow transplantation and as a therapeutic drug for various autoimmune diseases such as psoriasis and Behcet's disease and rheumatism, and that the compound can be prepared into an injection and used as a lytic agent such as polyethylene glycol and ethanol. However, polyethylene glycol has problems in its use because it has adverse effects such as local irritation and hemolysis. In addition, since ethanol also has local irritativeness, it is not suitable for injection.

When the above-mentioned compound, particularly 2-amino-2- [ 2- (4-octylphenyl) ethyl ] propane-1, 3-diol hydrochloride (hereinafter, also referred to as the present compound in the present specification) is dissolved in distilled water to prepare a liquid preparation, the liquid preparation has a problem of having hemolytic properties and local irritancy. In addition, even when a tonicity agent such as sodium chloride, which is an additive generally used in liquid preparations such as injections and eye drops, is added to a liquid preparation of the present compound, hemolysis and local irritativeness cannot be reduced, and thus it is still unsatisfactory.

JP-B-50-48485 discloses that lecithin, particularly egg yolk lecithin, is not hemolytic. However, this publication does not describe that the hemolytic activity of the active ingredient compound can be reduced. Further, Japanese patent application laid-open No. 6-340525 describes an eye drop for stabilizing a vitamin A compound and reducing irritation to the eye, which is characterized by containing a vitamin A compound, hydrogenated lecithin and a nonionic surfactant at a specific ratio. The main descriptions in this publication are: since the nonionic surfactant added to the vitamin A compound as an active ingredient has irritation to eyes, 0.1 to 1 part of hydrogenated lecithin is added to 1 part of the vitamin A compound and 0.01 to 1 part of the nonionic surfactant is added to reduce the irritation.

Description of the invention

In view of the above circumstances, the present inventors have made various studies to obtain a pharmaceutical composition containing 2-amino-2- [ 2- (4-octylphenyl) ethyl ] propane-1, 3-diol or a pharmaceutically acceptable acid addition salt thereof, which can be prepared into a liquid preparation such as an injection or an eye drop having few side effects such as hemolysis or the like or little local irritation, and as a result, have found that the object can be achieved by adding lecithin, and have completed the present invention.

That is, the present invention can provide a pharmaceutical composition characterized by adding a lecithin to 2-amino-2- [ 2- (4-octylphenyl) ethyl ] propane-1, 3-diol or a pharmaceutically acceptable acid addition salt thereof, which is easy to formulate and suitable for preparing a liquid preparation that can reduce side effects such as hemolysis and has little local irritation. Further, the present inventors have found that a liquid preparation composition further reduced in local irritation can be obtained by further adding a saccharide selected from a monosaccharide, a disaccharide and a sugar alcohol to the composition. The pharmaceutical composition of the present invention, for example, when prepared into an injection, can significantly reduce the irritation to the skin or blood vessels. Furthermore, the composition of the present invention can be added to the active ingredient compound 1 part by weight of lecithin in an amount of 5 parts by weight or more, usually 5 to 300 parts by weight, particularly 5 to 100 parts by weight, preferably 5 to 50 parts by weight, more preferably 5 to 20 parts by weight, and can significantly reduce hemolysis and local irritation of the active ingredient.

The pharmaceutical composition of the present invention comprises 2-amino-2- [ 2- (4-octylphenyl) ethyl ] propane-1, 3-diol or a pharmaceutically acceptable acid addition salt thereof as an active ingredient, and lecithin and, if necessary, a saccharide may be added thereto.

The active ingredient 2-amino-2- [ 2- (4-octylphenyl) ethyl ] propane-1, 3-diol or a pharmaceutically acceptable acid addition salt thereof in the pharmaceutical composition of the present invention can be produced according to the method described in International publication WO 94/08943. A preferred compound is 2-amino-2- [ 2- (4-octylphenyl) ethyl ] propane-1, 3-diol hydrochloride. Other acid addition salts such as hydrobromide, sulfate, acetate, fumarate, maleate, benzoate, citrate, malate, methanesulfonate, benzenesulfonate and the like.

The content of 2-amino-2- [ 2- (4-octylphenyl) ethyl ] propane-1, 3-diol or a pharmaceutically acceptable acid addition salt thereof is 0.01 to 20% by weight, particularly preferably 0.1 to 10% by weight, based on the total weight of the composition.

Examples of the lecithin to be used in the present invention include lecithin such as egg yolk lecithin and soybean lecithin, and hydrogenated lecithin. Among them, in order to increase the amount of the active ingredient compound dissolved and to obtain a liquid having high transparency, it is preferable that the lecithin has a high phosphatidylcholine content, and a small amount of lysophosphatidylcholine or phosphatidylethanolamine having a high iodine value can be detected. For example, in the case of egg yolk lecithin, it is preferable that the content of phosphatidylcholine be 65 to 95%, and that the composition contain a small amount of lysophosphatidylcholine, phosphatidylethanolamine, and iodine value of 60 to 80. Wherein the refined egg yolk lecithin in the specifications of the external use medicine of Japanese pharmacopoeia is most suitable. The hydrogenated lecithin refers to lecithin having increased oxidation resistance by hydrogenation, and specifically, hydrogenated egg yolk lecithin and hydrogenated soybean lecithin. The iodine value of these hydrogenated lecithins is preferably 6 or more. The content of lecithin used in the present invention is 5 parts by weight or more, usually 5 to 300 parts by weight, particularly 5 to 100 parts by weight, preferably 5 to 50 parts by weight, and more preferably 5 to 20 parts by weight, based on 1 part by weight of the active ingredient.

The saccharide used in the present invention may be selected from monosaccharides, disaccharides and sugar alcohols, and specific examples thereof include glucose, fructose, D-maltose, lactose, white sugar (sucrose), D-mannitol, D-xylitol and D-sorbitol, and 1 or more thereof may be used in combination. The content of these saccharides is 1 to 100 parts by weight, particularly preferably 5 to 80 parts by weight, based on 1 part by weight of 2-amino-2- [ 2- (4-octylphenyl) ethyl ] propane-1, 3-diol or a pharmaceutically acceptable acid addition salt thereof.

The pharmaceutical composition of the present invention is in the form of a liquid preparation, specifically, an injection, an eye drop, a nasal drop, an ear drop, an infusion solution, an oral liquid, a liquid preparation for inhalation, a liquid preparation for lotion, and the like, and preferably an injection (intravenous, subcutaneous, intramuscular), an eye drop, an infusion solution. Particularly preferred are injections (intravenous, subcutaneous, intramuscular) and infusion solutions. The form of these preparations can be appropriately selected depending on the indication, the symptoms thereof, sex and age of the patient, the place to which the preparation is applied, and the like, and the preparations can be prepared by methods known to those skilled in the art.

The pharmaceutical composition of the present invention may be marketed as a liquid preparation product, or may be marketed as a kit comprising a powder or a freeze-dried product containing an active ingredient or the like and a dissolving agent. For example, 2-amino-2- [ 2- (4-octylphenyl) ethyl ] propane-1, 3-diol or a pharmaceutically acceptable acid addition salt thereof (particularly, hydrochloride salt) as an active ingredient is dissolved in purified water, the resulting solution is aseptically filtered, filled in a vial, and then vacuum freeze-dried to prepare a freeze-dried product. On the other hand, the solution is an aqueous solution prepared by dissolving the lecithin and optionally the sugar used in the present invention in distilled water. The freeze-dried product can be dissolved in the solution at the time of use. The dissolved solution is used in an amount of 5 to 2000 times (parts by weight) relative to 2-amino-2- [ 2- (4-octylphenyl) ethyl ] propane-1, 3-diol or a pharmaceutically acceptable acid addition salt thereof. Among them, distilled water is preferably distilled water for injection in the case of an injection. The freeze-dried product can be usually filled in a vial, and can be stored at room temperature for a long period of time by introducing nitrogen gas, sealing with a rubber plug, or sealing with an aluminum seal. In addition, the freeze-dried product may contain both lecithin and optionally added saccharide and the active ingredient 2-amino-2- [ 2- (4-octylphenyl) ethyl ] propane-1, 3-diol or a pharmaceutically acceptable acid addition salt thereof, instead of adding lecithin and optionally added saccharide to the above-mentioned solution. The lecithin is contained in an amount of 5 parts by weight or more based on 1 part by weight of the active ingredient, and usually 5 to 300 parts by weight, particularly 5 to 100 parts by weight, preferably 5 to 50 parts by weight, and more preferably 5 to 20 parts by weight may be added. The amount of the saccharide to be added is 1 to 100 parts by weight, preferably 5 to 80 parts by weight, based on 1 part by weight of the active ingredient.

The pharmaceutical composition of the present invention may contain, in addition to the above-mentioned components, a solvent, an isotonic agent, a pH adjuster, a buffer, an antioxidant, a thickener, a surfactant, a preservative, a humectant, an aromatic agent, a coloring agent, and the like as appropriate. These additives may be added when the composition of the present invention is formulated, or may be added to a solution for dissolution when the above-mentioned kit preparation is used.

The pharmaceutical composition of the present invention can be used as a liquid preparation for suppressing rejection after organ or bone marrow transplantation or maintenance immunotherapy thereof, treating eye diseases such as Behcet's disease and uveitis, and treating dermatitis such as psoriasis, atopic dermatitis, contact dermatitis, and allergic dermatitis. More specifically, the composition of the present invention can be used for the treatment or prevention of various indications (immunosuppression in organ or bone marrow transplantation, various autoimmune diseases, various allergic diseases, etc.) which could not be treated or prevented by conventional oral preparations.

That is, the composition of the present invention can be used as a liquid preparation for the treatment and prevention of resistance or rejection to tissue transplantation (e.g., transplantation of heart, kidney, liver, lung, bone marrow, cornea, pancreas, small intestine, limbs, muscle, nerve, fat marrow, duodenum, skin, islet cells, etc., including xenotransplantation), graft versus host (GvH) disease caused by bone marrow transplantation, autoimmune disease, for example, chronic rheumatoid arthritis, systemic lupus erythematosus, nephrotic syndrome, hashimoto's goiter, multiple sclerosis, myasthenia gravis, type I diabetes, type II adult-onset diabetes, uveitis, nephrotic syndrome, steroid-dependent or steroid-resistant nephropathy, palmar-plantar hypothalamus, allergic encephalomyelitis, glomerulonephritis, and infections caused by pathogenic microorganisms. In addition, it is also useful for the treatment of inflammatory, proliferative and hyperproliferative skin diseases, as well as immune-mediated diseases which develop in the skin, such as psoriasis, psoriatic arthritis, atopic eczema (atopic dermatitis), contact dermatitis, also eczematous dermatitis, seborrheic dermatitis, lichen planus, pemphigus, vesicular pemphigus, epidermophytosis, urticaria, vascular edema, vasculitis, erythema, cutaneous eosinophilia, acne, alopecia areata, eosinophilic fasciitis, and atherosclerosis. More particularly, since the composition of the present invention can prevent hair loss, form hair buds and/or promote hair regrowth and growth, it can be used to treat female or male hair loss or senile hair loss, so that the hair can be restored.

The compositions of the invention may also be suitable for the treatment of respiratory diseases such as sarcoidosis, fibroid lung, idiopathic interstitial pneumonia, and reversible occlusive airway diseases such as bronchial asthma, pediatric asthma, allergic asthma, intrinsic asthma, extrinsic asthma, and dust asthma, particularly chronic or refractory asthma (e.g. delayed asthma and airway hypersensitivity), bronchitis, and the like. The compositions of the invention may also be used to treat liver disorders associated with anemia. But also for specific ocular diseases such as conjunctivitis, keratoconjunctivitis, keratitis, vernal mucositis, uveitis associated with Behcet's disease, keratitis, herpetic keratitis, keratoconus, corneal epithelial degeneration, corneal leukoplakia, ocular pemphigus, Moren's ulcer, scleritis, Graves ' disease, severe intraocular inflammation.

In addition, the compositions of the present invention may be used to treat or prevent inflammation of the mucosa or blood vessels (e.g., leukotriene B4-mediated diseases, gastric ulcers, ischemic diseases and vascular injury caused by thrombosis, ischemic bowel diseases, inflammatory bowel diseases (e.g., Crohn's disease and ulcerative colitis), necrotic enteritis), and intestinal injury associated with thermal burns. The composition of the present invention can also be used for treating or preventing interstitial nephritis, Goodpasture's syndrome, hemolytic uremic syndrome, diabetic nephropathy and other renal diseases; neuropathy such as polymyositis, Guillain-Barre syndrome, Meniere's disease, and radiculopathy; endocrine diseases such as hyperthyroidism and Basedow's disease; blood diseases such as pure erythrodysplasty, aplastic anemia, idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, agranulocytosis, and erythropoiesis incapability; bone diseases such as osteoporosis; respiratory airway diseases such as sarcoidosis, fibrotic lung and idiopathic interstitial pneumonia; dermatosis such as dermatomyositis, leukoplakia vulgaris, ichthyosis vulgaris, photosensitive dermatitis, and cutaneous T cell lymphoma; circulatory diseases such as arteriosclerosis, aortic inflammation, polyarteritis nodosa, and cardiomyopathy; collagen diseases such as scleroderma, Wegner's granulomatosis, and Sjogren's syndrome; obesity; eosinophilic fasciitis; periodontal disease; nephrotic syndrome; hemolytic uremic syndrome; and muscular dystrophy.

The compositions of the invention are also suitable for the treatment or prevention of intestinal inflammation/allergic reactions such as Coeliac disease, proctitis, eosinophilic gastroenteritis, mastocytosis, Crohn's disease and ulcerative colitis; and allergic diseases associated with food but whose symptoms are not directly related to the gastrointestinal tract, such as migraine, rhinitis and eczema.

Since the active ingredient 2-amino-2- [ 2- (4-octylphenyl) ethyl ] propane-1, 3-diol or a pharmaceutically acceptable acid addition salt thereof in the pharmaceutical composition of the present invention has liver regeneration activity and/or activity of promoting hepatocyte hypertrophy and hepatocyte proliferation, the composition of the present invention can be used for treating and preventing liver diseases such as immunogenic diseases (e.g., chronic autoimmune liver diseases such as autoimmune hepatitis, primary biliary cirrhosis and sclerosing cholangitis), partial liver resection, acute liver necrosis (e.g., necrosis caused by toxin, viral hepatitis, shock or hypoxia), viral hepatitis b, non-a/non-b hepatitis and cirrhosis.

In addition, the composition of the present invention can be used as an antibacterial composition, and thus can be used for treating diseases caused by pathogenic microorganisms and the like. Furthermore, the composition of the present invention can be used for the treatment or prevention of malignant joint rheumatism, amyloidosis, fulminant hepatitis, summer-de-rager's syndrome, pustular psoriasis, Behcet's disease, systemic erythema, endocrine ophthalmopathy, progressive systemic sclerosis, mixed connective tissue disease, aortic inflammation syndrome, Wegener's granulomatosis (Wegner's granulomatosis), active chronic hepatitis, Evans blue syndrome, pollinosis, idiopathic hypoparathyroidism, Addison's disease (autoimmune adrenalitis), autoimmune orchitis, autoimmune oophoritis, hemocyte condensing disease, paroxysmal cold hemoglobinuria, pernicious anemia, adult T cell leukemia, autoimmune atrophic gastritis, lupus nephritis, renal tubular nephritis, interstitial nephritis, and the like, Membranous nephritis, amyotrophic lateral sclerosis, rheumatic fever, post-myocardial infarction syndrome, and sympathetic ophthalmia.

The composition can also simultaneously use other immunosuppressants, steroid drugs (prednisolone, methylprednisolone, dexamethasone, hydrocortisone and the like) or non-steroidal anti-inflammatory drugs and the like according to different occasions. Other particularly preferred immunosuppressive agents may be selected from azathioprine, brequinar sodium salt, cyclosporin A, deoxyspergualin, mizoribine, zymolite 2-morpholinoethyl ester, rapamycin, tacrolimus monohydrate, leflunomide, and OKT-3.

The composition of the present invention may vary depending on the indication, the symptoms thereof, sex and age of a patient, the site to which the composition is applied, and the like, and a clinically favorable effect can be obtained by administering or applying a drug containing 0.00001 to 20% by weight, preferably 0.0001 to 10% by weight of the present compound 1 time or several times (for example, 2 to 5 times) a day.

Best mode for carrying out the invention

The present invention will be described in more detail below with reference to examples and comparative examples.

In the following examples and comparative examples, the proportions are based on weight unless otherwise specified. As described above, the present compound is 2-amino-2- [ 2- (4-octylphenyl) ethyl ] propane-1, 3-diol hydrochloride.

Example 1

An injection containing the present compound having the following composition was prepared.

0.03 percent of the compound

Refined egg yolk lecithin 1.0%

D-mannitol 5.0%

The composition is dissolved in distilled water for injection to prepare injection with total volume of 10 ml. If necessary, usual additives such as preservatives may be added.

Example 2

An injection containing the present compound having the following composition was prepared.

0.1 percent of the compound

1.0 percent of hydrogenated egg yolk lecithin

D-mannitol 5.0%

The composition is dissolved in distilled water for injection to prepare injection with total volume of 10 ml. If necessary, usual additives such as preservatives may be added.

Example 3

An injection containing the present compound having the following composition was prepared.

0.1 percent of the compound

Refined egg yolk lecithin 1.0%

The above composition is dissolved in distilled water for injection (optionally, common additives such as antiseptic can be added), sterile filtered, filled into a vial in a total amount of 10ml, and freeze-dried according to a conventional method to prepare an injection.

Example 4

An injection containing the present compound having the following composition was prepared.

0.1 percent of the compound

Hydrogenated soybean lecithin 1.0%

The above composition is dissolved in distilled water for injection (optionally, common additives such as antiseptic can be added), sterile filtered, filled into a vial in a total amount of 10ml, and freeze-dried according to a conventional method to prepare an injection.

Example 5

An injection containing the present compound having the following composition was prepared.

0.1 percent of the compound

Refined egg yolk lecithin 2.0%

0.9 percent of sodium chloride

The composition is dissolved in distilled water for injection to prepare injection with total volume of 10 ml. If necessary, usual additives such as preservatives may be added.

Example 6

An injection containing the present compound having the following composition was prepared.

0.01 percent of the compound

Refined egg yolk lecithin 0.05%

D-mannitol 5.0%

The composition is dissolved in distilled water for injection to prepare injection with total volume of 10 ml. If necessary, usual additives such as preservatives may be added.

Example 7

An injection containing the present compound having the following composition was prepared.

0.01 percent of the compound

Refined egg yolk lecithin 0.5%

D-mannitol 5.0%

The composition is dissolved in distilled water for injection to prepare injection with total volume of 10 ml. If necessary, usual additives such as preservatives may be added.

Example 8

An injection containing the present compound having the following composition was prepared.

0.1 percent of the compound

Refined egg yolk lecithin 0.6%

10.0 percent of white sugar

The above composition was dissolved in distilled water for injection, sterile-filtered, and then 2ml of the total amount was filled in a vial, and freeze-dried according to a conventional method to prepare an injection. If necessary, usual additives such as preservatives may be added.

Example 9

An injection containing the present compound having the following composition was prepared.

0.1 percent of the compound

Refined egg yolk lecithin 0.6%

D-mannitol 10.0%

Dissolving the above composition in distilled water for injection, sterile filtering, filling 10ml into small bottle, freeze drying according to conventional method, and making into injection. If necessary, usual additives such as preservatives may be added.

Example 10

An injection containing the present compound having the following composition was prepared.

0.01 percent of the compound

Refined egg yolk lecithin 1.0%

The composition is dissolved in distilled water for injection to prepare injection with total volume of 10 ml. If necessary, usual additives such as preservatives may be added.

Example 11

An injection containing the present compound having the following composition was prepared.

0.1 percent of the compound

Refined egg yolk lecithin 1.0%

D-mannitol 5.0%

The composition is dissolved in distilled water for injection to prepare injection with total volume of 10 ml. If necessary, usual additives such as preservatives may be added.

Example 12

The components described in examples 1 to 11 were dissolved in sterilized distilled water (if necessary, usual additives such as a preservative may be added) to prepare eye drops in a total amount of 10 ml.

Comparative example 1

0.1 percent of the compound

The composition is dissolved in distilled water for injection to prepare injection with total volume of 10 ml.

Comparative example 2

0.1 percent of the compound

0.9 percent of sodium chloride

The composition is dissolved in distilled water for injection to prepare injection with total volume of 10 ml.

Comparative example 3

0.03 percent of the compound

Mannitol 5.0%

The composition is dissolved in distilled water for injection to prepare injection with total volume of 10 ml.

Comparative example 4

0.01 percent of the compound

D-mannitol 5.0%

The composition is dissolved in distilled water for injection to prepare injection with total volume of 10 ml.

Comparative example 5

0.1 percent of the compound

Mannitol 5.0%

The composition is dissolved in distilled water for injection to prepare injection with total volume of 10 ml.

Experimental example 1

After 1.0ml of the test solution was kept at 37 ℃ for 2 minutes, 0.1ml of human blood containing heparin (10U/ml) was added and mixed. After 30 minutes at constant temperature, the mixture was cooled with water and centrifuged at 3000rpm for 5 minutes. The supernatant was diluted with physiological saline, and the absorbance at 540nm was measured by the method of Inglot et al (biochem. Pharmacol., Vol.17, p.269, 1986) to calculate the hemolysis rate. Distilled water for injection was used as a control. From the results of the calculation of the hemolysis ratio, it can be judged that the preparations of examples 1 to 10 can significantly reduce the hemolysis. In contrast, the preparations of comparative examples 1 to 4 were hemolytic.

Experimental example 2

The preparations of examples 1 and 11 and the preparations of comparative examples 3 and 5 were administered to 5-week-old LEW rats and intravenously repeatedly over 5 days, and the presence or absence of local irritation was confirmed using the tail swelling ratio { (administration group tail diameter-control group tail diameter) ÷ control group tail diameter × 100} as an index. From the results, it was found that the formulations of examples 1 and 11 had tail swelling rates of 0.5% and 0.7%, respectively, and significantly reduced local irritation. In contrast, the formulations of comparative examples 3 and 5 had tail swelling rates of 15.6% and 20.5%, respectively, and had local irritation.

Experimental example 3

The evaluation of the ocular irritation can be carried out according to the short-term test method of ocular irritation antiseptic ophthalmic mucosa irritation test in the scientific research report of the ministry of health (showa 45 years).

Industrial applicability

A pharmaceutical composition comprising 2-amino-2- [ 2- (4-octylphenyl) ethyl ] propane-1, 3-diol or a pharmaceutically acceptable acid addition salt thereof, wherein lecithin is added to the 2-amino-2- [ 2- (4-octylphenyl) ethyl ] propane-1, 3-diol or the pharmaceutically acceptable acid addition salt thereof, and optionally a saccharide is further added.

Claims (13)

1. A pharmaceutical composition for immunosuppressive therapy, comprising 2-amino-2- [ 2- (4-octylphenyl) ethyl ] propane-1, 3-diol or a pharmaceutically acceptable acid addition salt thereof as an active ingredient, and lecithins, wherein lecithin is contained in an amount of 5 to 100 parts by weight per 1 part by weight of the active ingredient.

2. A pharmaceutical composition for suppressing rejection in organ or bone marrow transplantation, for immunosuppressive maintenance therapy, or for preventing or treating autoimmune or allergic diseases, which comprises 2-amino-2- [ 2- (4-octylphenyl) ethyl ] propane-1, 3-diol or a pharmaceutically acceptable acid addition salt thereof as an active ingredient, and lecithins, wherein the lecithin is contained in an amount of 5 to 100 parts by weight per 1 part by weight of the active ingredient.

3. The pharmaceutical composition according to claim 1 or 2, wherein the lecithin is lecithin or hydrogenated lecithin.

4. The pharmaceutical composition according to claim 1 or 2, which may further comprise a saccharide.

5. The pharmaceutical composition according to claim 4, wherein the saccharide is 1 selected from a monosaccharide, a disaccharide or a sugar alcohol.

6. The pharmaceutical composition according to claim 5, wherein the saccharide is 1 selected from the group consisting of D-mannitol, glucose, D-xylitol, D-maltose, D-sorbitol, lactose, fructose and white sugar.

7. A pharmaceutical composition according to claim 1 or 2 wherein the active ingredient is 2-amino-2- [ 2- (4-octylphenyl) ethyl ] propane-1, 3-diol hydrochloride.

8. A kit comprising a lyophilized product of 2-amino-2- [ 2- (4-octylphenyl) ethyl ] propane-1, 3-diol or a pharmaceutically acceptable acid addition salt thereof, and a dissolution solution comprising an aqueous solution containing lecithin, wherein lecithin is contained in an amount of 5 to 100 parts by weight per 1 part by weight of the active ingredient.

9. A kit comprising a lyophilized product comprising 2-amino-2- [ 2- (4-octylphenyl) ethyl ] propane-1, 3-diol or a pharmaceutically acceptable acid addition salt thereof and lecithin, and a solution comprising distilled water, wherein lecithin is contained in an amount of 5 to 100 parts by weight per 1 part by weight of the active ingredient.

10. The kit according to claim 8, further comprising a saccharide in the lyophilized product and/or the dissolved solution.

11. The kit of claim 8 wherein the pharmaceutically acceptable salt of 2-amino-2- [ 2- (4-octylphenyl) ethyl ] propane-1, 3-diol is the hydrochloride salt.

12. The kit according to claim 9, further comprising a saccharide in the lyophilized product and/or the dissolved solution.

13. The kit of claim 9 wherein the pharmaceutically acceptable salt of 2-amino-2- [ 2- (4-octylphenyl) ethyl ] propane-1, 3-diol is the hydrochloride salt.