Polypeptide composition and application thereof in treating male erectile dysfunction

Abstract

The invention provides a polypeptide composition and application thereof in treating male erectile dysfunction. Specifically, the polypeptide composition contains the erectile peptide screened and identified by the invention, and the erectile peptide has good oxidation fatigue resistance, can effectively promote penile erection, improve testosterone level and effectively treat erectile dysfunction, and has wide application prospects.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of biology, more particularly to a polypeptide composition and its use in treating male erectile dysfunction. BACKGROUND

[0002] Impotence, also known as erectile dysfunction (ED), is the inability of a man to achieve and maintain a penile erection sufficient for satisfactory sexual performance. As a common disease affecting male sexual function, its incidence rate cannot be ignored. A Meta analysis in China concluded that the incidence rate of ED in men aged 40-49 was 40.48%. A report on the incidence rate of ED in men in Asia showed that the incidence rate of ED in Asia was quite wide.

[0003] The current treatment for impotence mainly relies on western medicine. The star drug is Sildenafil. Sildenafil is a V-type phosphodiesterase (PDE5) inhibitor. After oral absorption, it binds to the receptors of the corpus cavernosum smooth muscle. NO released by nerve endings binds to guanylate cyclase, stimulates guanosine triphosphate (GTP), and converts GTP into cyclic guanosine monophosphate (cGMP). cGMP is catalytically converted into cyclic monophosphate (CMP) by PDE, and cCMP is a vasodilator that causes the corpus cavernosum to become engorged with blood. Sildenafil can bind to PDE to inhibit the conversion of cCMP, increase the degree of corpus cavernosum engorgement, and achieve erection. The citrate preparation (Viagra: Viagra, produced by Pfizer, USA) has been approved by the FDA for marketing in the United States since March 1998. This product is considered to be the first safe and effective drug for the treatment of sexual dysfunction. In a study of 12 mixed impotent patients (36-63 years old) with different doses of oral Sildenafil, the penile root erection reached 80%, and the control group could last for 1.3 min. The drug group orally took 10, 25, and 50 mg, respectively, and could last for 3.5, 8.0, and 11.2 min, respectively. The penile tip erection reached 80%, and the control group could last for 1.2 min. The drug group orally took 50 mg and could last for 4 min.

[0004] In addition, there are other therapeutic drugs such as apomorphine. Apomorphine alkaloid was first extracted from a water salicylic tree tuber by Egyptians and Mayans, and was used as a drug for treating mental illness. It is now synthesized from morphine and is used for emesis, sedation, and desire, and is the latest for intractable Parkinson's disease. Apomorphine is a dopamine receptor agonist, and has an erection effect on healthy people or impotent patients, and by reducing the activity of central dopamine, the threshold of erection and ejaculation is lowered, but this effect can be blocked by central dopamine receptors. Apomorphine is usually administered by subcutaneous injection, and 0.25-1.0 mg can cause 60% of psychogenic impotent patients to have an erection, but 50% of patients have nausea. Instead, 3-4 mg of sublingual administration is used, the active ingredient is completely absorbed, 60%-80% of impotent patients can have an erection, and there are basically no side effects. The drug has a potential for addiction, and must be prescribed and the dosage must be reduced as much as possible. In addition, the therapeutic drug naltrexone. Naltrexone is a long-acting sedative antagonist that has the effect of expanding endogenous gonadotropin-releasing hormone and can inhibit the activity of sexual function antagonists to cause sexual impulses. Tests have shown that 50 mg of naltrexone taken orally daily can completely erect 20% of patients and all users have the morning erection phenomenon.

[0005] In addition, there is a polypeptide drug, calcitonin peptide. Calcitonin peptide relaxes smooth muscle by activating potassium ion channels on the membrane of smooth muscle cells and exciting cyclic adenosine monophosphate. After injection into the corpus cavernosum of the penis, it induces arterial vessel wall relaxation, increases blood flow, and relaxes the corpus cavernosum, causing venous vessels to close and causing an erection. A mixed preparation of 5 μg of calcitonin peptide and 110 μg of prostaglandin E1 is used for impotent patients who do not respond to papaverine or have incomplete closure of the penis. It can cause 70% of patients to have an erection, indicating that the polypeptide drug calcitonin peptide has a good effect on the treatment of impotence.

[0006] Although the prior art has many drugs that can be used for the treatment of impotence, these drugs have more or less side effects, such as sildenafil, which can lower the blood pressure of non-normal or normal people, and can cause fatal hypotension when used with nitrate drugs, but this has not prevented men who have not had sex for many years from abusing the drug in their quest for youth, resulting in the death of many men with cardiovascular disease. Therefore, the FDA has warned men with cardiovascular disease not to use it. The common adverse reactions of this drug are headache, facial flushing, indigestion, nasal congestion, diarrhea, dizziness, and rash, and less common visual disturbances, photosensitivity, and are related to the dose. Therefore, it is an important direction of research to develop a drug with fewer side effects and better therapeutic effect. SUMMARY

[0007] Research has shown that antioxidants can help protect the body from free radical damage, a contributing factor to health issues like impotence. By screening a peptide library, the researchers identified an erectile-enhancing peptide that possesses both erection-promoting and antioxidant properties.

[0008] In one aspect, the present invention provides an erectile peptide, the amino acid sequence of which is shown in SEQ ID NO: 1.

[0009] In another aspect, the present invention provides a polypeptide composition comprising the erectile peptide of the present invention, the amino acid sequence of which is shown in SEQ ID NO: 1. The polypeptide composition can be used to treat male erectile dysfunction.

[0010] Furthermore, the polypeptide compositions of the present invention may be in the form of tablets, oral formulations, or injections. Preferably, they may be in the form of oral solutions. Pharmaceutical formulations for oral administration include tablets, push-fit capsules made of gelatin, and sealed soft capsules made of gelatin and a plasticizer such as glycerol or sorbitol. Tablets may be made by compression or molding, optionally with one or more auxiliary ingredients. Compressed tablets may be prepared by compressing a free-flowing active ingredient, such as a powder or granules, in a suitable machine, optionally mixed with a binder, an inert diluent or lubricant, a surfactant, or a dispersant. Molded tablets may be prepared by molding a mixture of a powdered compound moistened with an inert liquid diluent in a suitable machine. Tablets may optionally be coated or scored and may be formulated to provide slow or controlled release of the active ingredient. All formulations for oral administration should be used in dosages suitable for such administration. Push-fit capsules may contain the active ingredient mixed with a filler such as lactose, a binder such as starch, and / or a lubricant such as talc or magnesium stearate, and optionally a stabilizer. In soft capsules, the active compound can be dissolved or suspended in a suitable liquid, such as a fatty oil, liquid paraffin or liquid polyethylene glycol. In addition, a stabilizer can be added. The core of the dragee has a suitable coating. To this end, a concentrated sugar solution can be used, which can optionally contain gum arabic, talc, polyvinyl pyrrolidone, carbomer gel, polyethylene glycol and / or titanium dioxide, a lacquer solution and a suitable organic solvent or solvent mixture. Dyes or pigments can be added to the tablet or dragee coating to identify or characterize different combinations of active compound dosages.

[0011] On the other hand, common excipients used in polypeptide compositions include solvents, fragrances, flavoring agents, clarifiers, and preservatives. These excipients can be added simultaneously or selectively. The solvent is essential, and water can be used. Different excipient combinations include sweeteners, fragrances, clarifiers, or preservatives, or a combination of sweeteners and preservatives, with a combination of sweeteners and preservatives being preferred. Some excipients have both sweetening and flavoring properties, so in these cases, only one excipient needs to be added.

[0012] Furthermore, the composition of the present invention also comprises an excipient. Examples of the excipient may include: anti-adherents (e.g., magnesium stearate, etc.); binders (e.g., sugars and their derivatives: disaccharides, sucrose, lactose; polysaccharides and their derivatives: starch, cellulose or modified cellulose, such as microcrystalline cellulose and cellulose derivatives, including cellulose ethers, such as hydroxypropyl cellulose; sugar alcohols, such as xylitol, sorbitol or mannitol; proteins: gelatin; synthetic polymers: polyvinyl pyrrolidone or PVP, polyethylene glycol or PEG, polyvinyl pyrrolidone, starch, sucrose and polyethylene glycol, methylcellulose); coating agents (e.g., cellulose ether hydroxypropyl methylcellulose, synthetic polymers, shellac, zein zein or other polysaccharides, gelatin); enteric solvents (fatty acids, waxes, shellac, Plastics and plant fibers); colorants (titanium oxide, azo dyes, etc.); disintegrants (e.g., cross-linked polymers: cross-linked polyvinyl pyrrolidone such as cross-linked povidone, cross-linked sodium carboxymethyl cellulose or cross-linked sodium carboxymethyl cellulose, glycolate, etc.); flavoring agents (fruit extracts, etc.); glidants (e.g., fumed silica, talc, and magnesium carbonate, etc.); lubricants (e.g., talc or silica, and fats such as vegetable stearin, magnesium stearate, or stearic acid, etc.); preservatives (e.g., antioxidants such as vitamin A, vitamin E, vitamin C, retinyl palmitate, and selenium; cysteine, methionine; citric acid, sodium citrate; parabens: methyl paraben and propyl paraben); adsorbents; sweeteners Flavoring agents (such as sugar); vehicles (petrolatum, dimethyl sulfoxide, mineral oil, etc.); emollients / hardeners (carnauba wax, cetyl alcohol, cetyl ester wax, emulsifying wax, aqueous lanolin, lanolin, lanolin alcohol, microcrystalline wax, paraffin, petrolatum, polyethylene glycol, stearic acid, stearyl alcohol, white wax, yellow wax, etc.); emulsifiers / emulsifying agents / solubilizers (polysorbate 20, polysorbate 80, polysorbate 60, poloxamer, emulsifying wax, sorbitan monostearate, sorbitan monooleate, sodium lauryl sulfate, propylene glycol monostearate, diethylene glycol monoethyl ether, docusate sodium, etc.); humectants (such as glycerin, propylene glycol, polyethylene glycol, sorbitol solution, 1,2,6-hexanetriol, etc.); thickeners / gelling agents (carbomer, methyl parabens, etc.); cellulose, sodium carboxymethylcellulose, carrageenan, colloidal silicon dioxide, guar gum, hydroxypropyl cellulose, hydroxypropyl methylcellulose, gelatin, polyethylene oxide, alginic acid, sodium alginate, fumed silica, etc.); preservatives (benzoic acid, propylparaben, methylparaben, imidurea, sorbic acid, potassium sorbate, benzalkonium chloride, phenylmercuric acetate, chlorobutanol, phenoxyethanol, etc.); penetration enhancers (propylene glycol, ethanol, isopropyl alcohol, oleic acid, polyethylene glycol, etc.); chelating agents (ethylenediaminetetraacetic acid, etc.); acidifying / alkalinizing / buffering agents (citric acid, phosphoric acid, sodium hydroxide, sodium dihydrogen phosphate, trihydroxyamine, etc.); vehicle / solvent (purified water, hexylene glycol, propylene glycol, oleyl alcohol, propylene carbonate, mineral oil, etc.).The examples are numerous and different excipients may be used for different reasons and may have dual or multiple functions.

[0013] For the composition, preferably, the sweetener is selected from one or more of proteose, xylitol, aspartame and sucralose. For the composition, preferably, the preservative is selected from one or more of parabens, butylated hydroxyanisole, butylated hydroxytoluene and sorbic acid.

[0014] The preservative may be p-hydroxybenzoic acid ester, butylated hydroxytoluene, or sorbic acid, preferably butylated hydroxytoluene. Combinations of these may also be used, such as a combination of a p-hydroxybenzoic acid ester and butylated hydroxytoluene, or a combination of butylated hydroxytoluene and sorbic acid, or a combination of p-hydroxybenzoic acid ester, butylated hydroxytoluene, and sorbic acid. For the composition, the fragrance is preferably a fruit flavor.

[0015] Preferably, the clarifier is chitosan and gelatin, or a mixture of the two.

[0016] Preferably, the diluent is one or more of cellulose and inorganic salts, such as microcrystalline cellulose, calcium sulfate, calcium hydrogen phosphate, medicinal calcium carbonate, mannitol, etc., to increase the volume of the raw material and facilitate its molding.

[0017] Preferably, the binder is one or more of water, ethanol, sodium carboxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, gelatin and polyvinyl pyrrolidone.

[0018] Preferably, the lubricant is one or more of magnesium stearate, micronized silica gel, talc, hydrogenated vegetable oil, polyethylene glycol and magnesium lauryl sulfate.

[0019] Preferably, the disintegrant is one or more of low-substituted hydroxypropyl, cross-linked polyvinyl pyrrolidone and cross-linked sodium carboxymethyl cellulose.

[0020] Furthermore, the composition of the present invention can be in the form of granules. These granules can be swallowed directly or diluted with warm water for drinking, making them convenient to use and carry, and exhibiting rapid dissolution and absorption. The formulation excipients used for granules are similar to those used for tablets, including one or more of a filler, binder, wetting agent, disintegrant, lubricant, and film coating material.

[0021] For granules, preferably, the filler is one or more of cellulose and inorganic salts, such as microcrystalline cellulose, calcium sulfate, calcium hydrogen phosphate, pharmaceutical calcium carbonate, mannitol, etc., to increase the volume of the raw materials and facilitate their formation.

[0022] For granules, preferably, the binder is one or more of water, ethanol, sodium carboxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, gelatin and polyvinyl pyrrolidone.

[0023] For granules, preferably, the wetting agent is water or ethanol or a mixture of the two, for example, one or more of magnesium stearate, micronized silica gel, talc, hydrogenated vegetable oil, polyethylene glycol and magnesium lauryl sulfate.

[0024] For granules, preferably, the disintegrant is one or more of low-substituted hydroxypropyl, cross-linked polyvinyl pyrrolidone and cross-linked sodium carboxymethyl cellulose.

[0025] For granules, preferably, the film coating material is one or more of hydroxypropyl methylcellulose, polyethylene glycol, cellulose acetate phthalate and polyvinyl acetal diethylamine acetate.

[0026] Beneficial effects

[0027] The present invention provides a polypeptide composition and its use in treating male erectile dysfunction. Specifically, the polypeptide composition contains an erectile peptide screened and identified by the present invention. This erectile peptide has excellent antioxidant properties and can effectively promote penile erections, increase testosterone levels, and effectively treat erectile dysfunction, thus having broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 Effects of erectile peptide on serum testosterone levels in rats

[0029] Figure 2 Effects of erectile peptide on ICPmax of rat penis DETAILED DESCRIPTION

[0030] Those skilled in the art can refer to the contents of this article and appropriately improve the process parameters to achieve it. It is particularly important to point out that all similar replacements and modifications are obvious to those skilled in the art and are considered to be included in the present invention. The methods and applications of the present invention have been described through preferred embodiments, and relevant personnel can obviously change or appropriately change and combine the methods and applications described herein without departing from the content, spirit and scope of the present invention to achieve and apply the technology of the present invention. The methods, equipment, and materials in the following implementation cases, if not otherwise specified, are conventional methods, equipment, and materials in the art and can be purchased from the market.

[0031] Example 1 Anti-fatigue experiment of erectile peptide

[0032] The erection peptide of SEQ ID NO: 1 identified by the inventors according to peptide library screening is commissioned by Qiangyao Biology to be artificially synthesized, with a purity of 98.5% and a concentration of 10 mg / mL for standby.

[0033] SPF level male mice (body weight 18-20 g, Beijing Weitonglihua Experimental Animal Technology Co., Ltd.). After the mice were adapted for 1 week, they were randomly divided into 4 groups (n=10), respectively, blank control group (gargling with the same dose of 0.9% normal saline), low-dose group (10 mg / kg), medium-dose group (50 mg / kg), high-dose group (100 mg / kg). Each group was given by gavage, once a day, for 4 weeks. During the gavage period, they could eat and drink freely. 30 min after the last gavage, the mice were placed in a 45 cm x 52 cm x 45 cm swimming box (water depth 30 cm, water temperature 25℃) with a 5% body weight lead at the root of the tail, and were driven with a glass rod. The time from the start of swimming to the complete submersion in water for 10 s was recorded, which was the exhaustive exercise time. The results are shown in Table 1.

[0034] Table 1 Effect of erection peptide on exhaustive swimming time of mice

[0035] Group Exhaustive swimming time (s) Blank control group 330.5±23.8 Low-dose group 470.8±28.4 Medium dose group 568.2±31.7 High-dose group 605.4±34.2

[0036] The improvement of exercise tolerance is the most direct manifestation of the enhancement of anti-fatigue ability, and the length of swimming time can reflect the degree of animal exercise fatigue. As can be seen from Table 1, compared with the blank control group, the exhaustive swimming time of mice in different dose groups was significantly enhanced (P<0.05), and had good dose dependence, but obviously, the growth effect of the high-dose group was not too significant, and the medium-dose cost performance was the best, which could be effectively used in subsequent experiments. This shows that the erection peptide itself has good anti-fatigue effect.

[0037] The mice in each group were taken out of the swimming box, the hair was blown dry, and then the head was cut off to take blood, the serum was separated, and the BLA, BUN and other related biochemical indicators were measured according to the kit method. The results are shown in Table 2.

[0038] Table 2 Effect of erection peptide on BLA and BUN of mice

[0039] Group BLA (mmol / L) BUN (mmol / L) Blank control group 10.48±0.29 9.18±0.47 Low-dose group 9.53±0.34 8.42±0.34 Medium dose group 8.27±0.21 7.20±0.28 High-dose group 8.10±0.35 7.13±0.45

[0040] During intense exercise, the body's tissues and organs function through the lactic acid system. The higher the BLA content, the more likely the body is to produce fatigue as the degree of exercise increases. The higher the BUN content, the worse the body's high-load adaptability. As can be seen from Table 2, with the increase of the dose, the BLA and BUN of the treatment group are significantly lower than those of the blank control group, which fully shows that the erection peptide can effectively reduce the content of BLA and BUN, and has good anti-fatigue effect.

[0041] Example 2: Verification of the efficacy of erectile peptide on rat mating function

[0042] Nine-week-old healthy SD rats (weighing 250-280g) were taken and fed normally for 1 week. Female rats underwent bilateral ovariectomy and underwent the experiment 2 weeks after surgery. 48 hours before the experiment, 20μg of estradiol benzoate injection was subcutaneously injected per rat, and 4 hours before the experiment, 500μg of progesterone injection was subcutaneously injected per rat. Male rats were randomly divided into 4 groups according to body weight, with 10 rats in each group. Blank control group: 5mL·kg distilled water -1 , Erectile peptide low dose group: 10 mg·kg -1 , Erectile peptide medium dose group: 50mg·kg -1 , positive control group: sildenafil group 10 mg·kg -1 All the mice were gavaged once a day for 20 consecutive days.

[0043] Each male rat was placed in a cage alone for 10 minutes to allow it to adapt to the new environment. Then one female rat was added to each cage, and the following indicators were recorded: the time from the female rat being put into the cage to the first time the male rat caught the female rat (capture latency); the time from the female rat being put into the cage to the first time the male rat ejaculated (ejaculation latency); the results are shown in Table 3.

[0044] Table 3 Effects of erectile peptide on sexual function of rats

[0045] Group Capture latency / s Ejaculation latency period / s Blank control group 352.7±35.7 1089.1±103.2 Erectile peptide low dose group 190.4±27.8 714.8±53.7 Erectile peptide medium dose group 121.3±36.9 600.3±48.6 Positive control group 208.4±19.3 648.7±52.1

[0046] From the results in Table 3, it can be seen that compared with the blank control group, the three treatment groups can significantly reduce the capture latency and ejaculation latency, which shows that erectile peptide can significantly improve the sexual function of rats.

[0047] Example 3 Effect of erectile peptide on serum testosterone levels in rats

[0048] Nine-week-old healthy male SD rats (weighing 250-280 g) were fed normally for one week and randomly divided into four groups according to their body weight, with 10 rats in each group. -1 , Erectile peptide low dose group: 10 mg·kg -1 , Erectile peptide medium dose group: 50mg·kg -1 , positive control group: sildenafil group 10 mg·kg -1 All animals were gavaged once daily for 60 consecutive days. Blood was collected before the experiment to measure serum testosterone levels. 24 hours after the last administration of the drug, blood was collected from the tail artery, serum was separated, and serum testosterone levels were measured again. The results are as follows: Figure 1 shown.

[0049] from Figure 1As shown, compared with the blank control group, the low-dose and high-dose erectile peptide groups were able to significantly increase testosterone levels. The testosterone level of the medium-dose erectile peptide group reached (12.92±0.13) nmol / L. In the positive control group, there was no significant difference in testosterone levels before and after sildenafil administration, nor was there a significant difference compared with the blank control group, indicating that sildenafil could not significantly improve testosterone levels. This result shows that erectile peptide can significantly increase testosterone levels, thereby improving the sexual ability of rats.

[0050] Example 4 Effects of Erectile Peptide on Erectile Function in Rats

[0051] Nine-week-old healthy male Sprague-Dawley rats (weighing 250-280 g) were fed normally for one week and a vascular ED rat model was established by bilateral ligation of the internal iliac arteries. For the sham-operated group, rats were secured on an operating table and a midline incision was made in the lower abdomen. After opening the abdominal cavity, the bilateral internal iliac arteries were located and exposed without ligation. The abdominal viscera were then repositioned, and the peritoneum, muscle, subcutaneous fat, and skin were sutured sequentially.

[0052] The rats of vascular ED model were randomly divided into 10 groups (model group, positive control group, experimental group). The rats in the positive control group were gavaged with 10 mg·kg -1 The experimental group was given erectile peptide at a concentration of 10 mg kg daily by gavage. -1 ; Rats in the model group and sham operation group were not intervened, and only received an equal amount of normal saline by oral gavage every day. After 4 weeks of continuous oral gavage, penile erection was induced by stimulating the rat's cavernous nerve. The maximum intracavernous pressure ICPmax of the penis was measured using the RM-6280XC multi-channel physiological signal acquisition and processing system to evaluate the rat's erectile function. The same method was used to continuously stimulate the cavernous nerve of the penis twice, with an interval of 10 minutes between the two times. The ICPmax measured after the second stimulation was used as the penile ICPmax data of the rat. The results were averaged. The results are shown in Figure 2 shown.

[0053] from Figure 2 As can be seen, the ICPmax values ​​of the positive control group and the model group were significantly higher than those of the model group (P<0.01). The ICPmax value of the experimental group (54.31±2.12) mmHg was also higher than that of the positive control group (45.82±1.85) mmHg, and closer to that of the sham operation group; this proves that erectile peptide can improve the erectile function of model mice and has a good therapeutic effect.

[0054] Although various illustrative embodiments have been described above, any of a variety of changes may be made to the various embodiments without departing from the scope of the present invention as described in the claims. For example, in alternative embodiments, the order in which the various method steps described are performed may often be changed, while in other alternative embodiments, one or more method steps may be skipped. Optional features of various device and system embodiments may be included in some embodiments and not included in other embodiments. Therefore, the foregoing description is provided primarily for illustrative purposes and should not be construed as limiting the scope of the present invention, as set forth in the claims.

[0055] The embodiments and illustrations included herein show the specific embodiments that the subject matter of the present invention can be implemented by way of illustration and not limitation. As mentioned, other embodiments can be used and other embodiments can be derived therefrom, so that structural and logical replacement and change can be carried out without departing from the scope of the present disclosure. Only for convenience, these embodiments of the subject matter of the present invention can be referred to individually or collectively with the term "invention" herein, without intending to limit the scope of the application to any single invention or inventive concept (if the present invention in fact discloses multiple). Therefore, although specific embodiments have been illustrated and described herein, any scheme calculated for achieving the same purpose can replace the specific embodiments shown. The present disclosure is intended to cover any and all modifications or variations of various embodiments. By reading the above description, the combination of the above embodiments and other embodiments not specifically described herein will be apparent to those skilled in the art.

Claims

1. An erection peptide, characterized in that The amino acid sequence of the erectile peptide is shown in SEQ ID NO:

1.

2. A polypeptide composition, characterized in that Contains erectile peptide, the erectile peptide amino acid sequence is shown as SEQ ID NO:

1.

3. Use of an erectile peptide in preparing a polypeptide composition for treating male erectile dysfunction, wherein the amino acid sequence of the erectile peptide is shown in SEQ ID NO:

1.

4. The use according to claim 3, characterized in that The polypeptide composition is in the form of tablets.

5. The use according to claim 3, characterized in that The polypeptide composition is in the form of oral dosage form.

6. The method according to claim 4 or 5, characterized in that The polypeptide composition further contains a pharmaceutically acceptable carrier.

7. The use according to claim 6, characterized in that The polypeptide composition further contains a pharmaceutically acceptable carrier.

Images